This research project is part of a larger effort to develop and investigate optical coherence tomography (OCT) imaging technology for applications in gastrointestinal (Gl) endoscopy for the primary purpose of detecting dysplasia in common human pre-malignant Gl conditions. Dysplasia is the precursor of cancer in a number of Gl disorders, and is fundamentally a microscopic diagnosis based on specific changes in the cells and architecture of the mucosa. A key problem is that dysplastic Gl mucosa is usually not detectable by standard Gl endoscopy. Recent studies by the investigators have demonstrated that endoscopic OCT (EOCT) is capable of imaging Gl mucosa with unprecedented resolution and quality, and that the potential is strong for EOCT to become a powerful tool for diagnosis of dysplastic lesions. A significant limitation of the current EOCT prototype, however, is its limited field of view. It is not capable of imaging the entire circumference of the lumen of the gut, and is therefore not suitable for surveillance applications where comprehensive coverage of a segment of lumen is desirable. This proposal is focused on development and establishment of EOCT technology that will enable clinical trials of EOCT as a tool for surveillance in patients with premalignant Gl conditions. Dysplasia in Barrett's Esophagus is the primary clinical target for this project, and aberrant colonic crypt foci are the secondary target. The specific aims are: (1) to develop a new generation EOCT engine featuring improved resolution, improved image acquisition speed, and digital signal processing; (2) to develop EOCT probes to improve image resolution and to enable pull-back surveillance procedures; and (3) to refine the criteria for EOCT classification of dysplasia and develop efficient and accurate computeraided diagnosis (CAD) algorithms. The technology will be developed incrementally and will be rigorously characterized and calibrated and will be validated by careful in vitro and in vivo studies. Successful completion of this project will enable the clinical evaluation of technology that is expected to significantly improve the capacity to detect pre-malignant or early malignant lesions in the Gl tract and allow early therapeutic interventions that will positively impact on patient care and survival.